Ferroptosis: a new strategy for Chinese herbal medicine treatment of diabetic nephropathy

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. It has become a leading cause of death in patients with diabetes and end-stage renal disease. Ferroptosis is a newly discovered pattern of programmed cell death. Its main manifestation is the excessive accumulation of intracellular iron ion-dependent lipid peroxides. Recent studies have shown that ferroptosis is an important driving factor in the onset and development of DN. Ferroptosis is closely associated with renal intrinsic cell (including renal tubular epithelial cells, podocytes, and mesangial cells) damage in diabetes. Chinese herbal medicine is widely used in the treatment of DN, with a long history and definite curative effect. Accumulating evidence suggests that Chinese herbal medicine can modulate ferroptosis in renal intrinsic cells and show great potential for improving DN. In this review, we outline the key regulators and pathways of ferroptosis in DN and summarize the herbs, mainly monomers and extracts, that target the inhibition of ferroptosis.

[1]  Peng Xu,et al.  [Leonurine inhibits ferroptosis in renal tubular epithelial cells by activating p62/Nrf2/HO-1 signaling pathway]. , 2023, Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica.

[2]  W. Liu,et al.  Cytoplasmic HMGB1 induces renal tubular ferroptosis after ischemia/reperfusion. , 2023, International immunopharmacology.

[3]  S. M. Khadrawy,et al.  Umbelliferone attenuates diabetic cardiomyopathy by suppression of JAK/STAT signaling pathway through amelioration of oxidative stress and inflammation in rats , 2023, Journal of biochemical and molecular toxicology.

[4]  Xiaoyan Zhao,et al.  Berberine hydrochloride alleviates imatinib mesylate - induced cardiotoxicity through the inhibition of Nrf2-dependent ferroptosis. , 2023, Food & function.

[5]  Ke Li,et al.  Platycodin D ameliorates hyperglycaemia and liver metabolic disturbance in HFD/STZ-induced type 2 diabetic mice. , 2023, Food & function.

[6]  Chengyan Zhou,et al.  "Multiomics" Analyses Combined with Systems Pharmacology Reveal the Renoprotection of Mangiferin Monosodium Salt in Rats with Diabetic Nephropathy: Focus on Improvements in Renal Ferroptosis, Renal Inflammation, and Podocyte Insulin Resistance. , 2022, Journal of agricultural and food chemistry.

[7]  Zhongming Wu,et al.  Aspirin mediates protection from diabetic kidney disease by inducing ferroptosis inhibition , 2022, PloS one.

[8]  S. Nie,et al.  Advances in Polygonatum sibiricum polysaccharides: Extraction, purification, structure, biosynthesis, and bioactivity , 2022, Frontiers in Nutrition.

[9]  Jing Chen,et al.  Ginkgolide B alleviates oxidative stress and ferroptosis by inhibiting GPX4 ubiquitination to improve diabetic nephropathy. , 2022, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[10]  Y. Wan,et al.  Inhibition of ferroptosis of renal tubular cells with total flavones of Abelmoschus manihot alleviates diabetic tubulopathy , 2022, Anatomical record.

[11]  Tao Liu,et al.  Identification of Markers for Diagnosis and Treatment of Diabetic Kidney Disease Based on the Ferroptosis and Immune , 2022, Oxidative medicine and cellular longevity.

[12]  Eman Said,et al.  Calycosin modulates NLRP3 and TXNIP-mediated pyroptotic signaling and attenuates diabetic nephropathy progression in diabetic rats; An insight. , 2022, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[13]  Chunze Zhang,et al.  Platycodin D sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway , 2022, Frontiers in Oncology.

[14]  Min Chen,et al.  Glutathione Peroxidase 4 Is a Predictor of Diabetic Kidney Disease Progression in Type 2 Diabetes Mellitus , 2022, Oxidative medicine and cellular longevity.

[15]  Zhangsuo Liu,et al.  NLRP3-mediated pyroptosis in diabetic nephropathy , 2022, Frontiers in Pharmacology.

[16]  Xiaomei Zhang,et al.  Protective Effect of Berberine in Diabetic Nephropathy: A Systematic Review and Meta-Analysis Revealing the Mechanism of Action. , 2022, Pharmacological research.

[17]  D. Saigusa,et al.  Nrf2 deficiency deteriorates diabetic kidney disease in Akita model mice , 2022, Redox biology.

[18]  Yan Chen,et al.  Research progress on ferroptosis in diabetic kidney disease , 2022, Frontiers in Endocrinology.

[19]  Qiang Hua,et al.  Circ ASAP2 decreased inflammation and ferroptosis in diabetic nephropathy through SOX2/SLC7A11 by miR-770-5p , 2022, Acta Diabetologica.

[20]  Xu Zhang,et al.  Heme oxygenase-1 modulates ferroptosis by fine-tuning levels of intracellular iron and reactive oxygen species of macrophages in response to Bacillus Calmette-Guerin infection , 2022, Frontiers in Cellular and Infection Microbiology.

[21]  Xu Song,et al.  The Antivirulence Activity of Umbelliferone and Its Protective Effect against A. hydrophila-Infected Grass Carp , 2022, International journal of molecular sciences.

[22]  A. Farooqi,et al.  Regulation of Ferroptosis by Non-Coding RNAs: Mechanistic Insights , 2022, The Journal of Pharmacology and Experimental Therapeutics.

[23]  Shidong Zhang,et al.  Anti-Inflammation and Anti-Pyroptosis Activities of Mangiferin via Suppressing NF-κB/NLRP3/GSDMD Signaling Cascades , 2022, International journal of molecular sciences.

[24]  M. Zhang,et al.  Polygonatum sibiricum Polysaccharides Attenuate Lipopoly-Saccharide-Induced Septic Liver Injury by Suppression of Pyroptosis via NLRP3/GSDMD Signals , 2022, Molecules.

[25]  Yafeng Li,et al.  Trametenolic Acid Ameliorates the Progression of Diabetic Nephropathy in db/db Mice via Nrf2/HO-1 and NF-κB-Mediated Pathways , 2022, Journal of immunology research.

[26]  Meng-yuan Zhou,et al.  Umbelliferone Inhibits Migration, Invasion and Inflammation of Rheumatoid Arthritis Fibroblast-Like Synoviocytes and Relieves Adjuvant-Induced Arthritis in Rats by Blockade of Wnt/β-Catenin Signaling Pathway. , 2022, The American journal of Chinese medicine.

[27]  Qinhui Liu,et al.  Immune responses in diabetic nephropathy: Pathogenic mechanisms and therapeutic target , 2022, Frontiers in Immunology.

[28]  Maodi Xu,et al.  Schisandrin A from Schisandra chinensis Attenuates Ferroptosis and NLRP3 Inflammasome-Mediated Pyroptosis in Diabetic Nephropathy through Mitochondrial Damage by AdipoR1 Ubiquitination , 2022, Oxidative medicine and cellular longevity.

[29]  Weiguang Zhang,et al.  Influence of zinc levels and Nrf2 expression in the clinical and pathological changes in patients with diabetic nephropathy , 2022, Nutrition & Diabetes.

[30]  Qi Chen,et al.  12/15-Lipoxygenase Regulation of Diabetic Cognitive Dysfunction Is Determined by Interfering with Inflammation and Cell Apoptosis , 2022, International journal of molecular sciences.

[31]  Irina Ingold,et al.  GPX4: old lessons, new features. , 2022, Biochemical Society transactions.

[32]  A. Patzak,et al.  ZIP14 is involved in iron deposition and triggers ferroptosis in diabetic nephropathy. , 2022, Metallomics : integrated biometal science.

[33]  X. Liu,et al.  Identification of Genes Reveals the Mechanism of Cell Ferroptosis in Diabetic Nephropathy , 2022, Frontiers in Physiology.

[34]  Junxian Chen,et al.  Glabridin, a bioactive component of licorice, ameliorates diabetic nephropathy by regulating ferroptosis and the VEGF/Akt/ERK pathways , 2022, Molecular medicine.

[35]  Di Huang,et al.  Calycosin plays a protective role in diabetic kidney disease through the regulation of ferroptosis , 2022, Pharmaceutical biology.

[36]  Zhou Zhongyin,et al.  Isoliquiritin apioside relieves intestinal ischemia/reperfusion-induced acute lung injury by blocking Hif-1α-mediated ferroptosis. , 2022, International immunopharmacology.

[37]  Xuan Zhao,et al.  Resveratrol mediates the miR-149/HMGB1 axis and regulates the ferroptosis pathway to protect myocardium in endotoxemia mice. , 2022, American journal of physiology. Endocrinology and metabolism.

[38]  Jianzhao Liao,et al.  NAC alleviative ferroptosis in diabetic nephropathy via maintaining mitochondrial redox homeostasis through activating SIRT3-SOD2/Gpx4 pathway. , 2022, Free radical biology & medicine.

[39]  Pearl A. Sutter,et al.  The Cellular Senescence Factor Extracellular HMGB1 Directly Inhibits Oligodendrocyte Progenitor Cell Differentiation and Impairs CNS Remyelination , 2022, Frontiers in Cellular Neuroscience.

[40]  Cheng Wang,et al.  A review: Pharmacology and pharmacokinetics of Schisandrin A , 2022, Phytotherapy research : PTR.

[41]  Zhe-zhi Wang,et al.  Structural characterization and antioxidant activity of Polygonatum sibiricum polysaccharides. , 2022, Carbohydrate polymers.

[42]  Alaa Shafie,et al.  Vitamin D and Hypoxia-Inducible Factor (HIF-1α) Serum Levels as Markers for Progression of Nephropathy in Type 2 Diabetic Patients. , 2022, Clinical laboratory.

[43]  A. Mahmoud,et al.  Umbelliferone prevents isoproterenol-induced myocardial injury by upregulating Nrf2/HO-1 signaling, and attenuating oxidative stress, inflammation, and cell death in rats. , 2022, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[44]  Cheng Chen,et al.  Umbelliferone delays the progression of diabetic nephropathy by inhibiting ferroptosis through activation of the Nrf-2/HO-1 pathway. , 2022, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[45]  Jinzhong Huang,et al.  Platycodin D regulates high glucose-induced ferroptosis of HK-2 cells through glutathione peroxidase 4 (GPX4) , 2022, Bioengineered.

[46]  Haijian Wu,et al.  Cepharanthine Attenuates Early Brain Injury after Subarachnoid Hemorrhage in Mice via Inhibiting 15-Lipoxygenase-1-Mediated Microglia and Endothelial Cell Ferroptosis , 2022, Oxidative medicine and cellular longevity.

[47]  C. Hao,et al.  Cyclooxygenase-2 contributes to diabetic nephropathy through glomerular EP4 receptor. , 2022, Prostaglandins & other lipid mediators.

[48]  W. Ding,et al.  Leonurine attenuates cisplatin nephrotoxicity by suppressing the NLRP3 inflammasome, mitochondrial dysfunction, and endoplasmic reticulum stress , 2022, International Urology and Nephrology.

[49]  Md Jamal Uddin,et al.  Renoprotective Effects of Mangiferin: Pharmacological Advances and Future Perspectives , 2022, International journal of environmental research and public health.

[50]  Yan Liang,et al.  The management of diabetes mellitus by mangiferin: advances and prospects. , 2022, Nanoscale.

[51]  Saroj Arora,et al.  Protective effect of vanillic acid against diabetes and diabetic nephropathy by attenuating oxidative stress and upregulation of NF‐κB, TNF‐α and COX‐2 proteins in rats , 2022, Phytotherapy research : PTR.

[52]  H. Gerstein,et al.  Advanced Glycation End Products Predict Loss of Renal Function and High-Risk Chronic Kidney Disease in Type 2 Diabetes. , 2022, Diabetes care.

[53]  Gladys Thomas,et al.  Therapeutic Advances in Diabetic Nephropathy , 2022, Journal of clinical medicine.

[54]  Yue-xuan Wu,et al.  Activation of SSAT1/ALOX15 Axis Aggravates Cerebral Ischemia/Reperfusion Injury via Triggering Neuronal Ferroptosis , 2022, Neuroscience.

[55]  Li Han,et al.  Leonurine Preconditioning Attenuates Ischemic Acute Kidney Injury in Rats by Promoting Nrf2 Nuclear Translocation and Suppressing TLR4/NF-κB Pathway. , 2022, Chemical & pharmaceutical bulletin.

[56]  Junhua Li,et al.  Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients: a double blinded placebo controlled randomized study , 2021, Gut microbes.

[57]  B. Duncan,et al.  IDF diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045 , 2021, Diabetes Research and Clinical Practice.

[58]  Bin Wu,et al.  Berberine alleviates liver fibrosis through inducing ferrous redox to activate ROS-mediated hepatic stellate cells ferroptosis , 2021, Cell death discovery.

[59]  A. Rauf,et al.  Berberine as a Potential Anticancer Agent: A Comprehensive Review , 2021, Molecules.

[60]  Yuhua Wei,et al.  The role of non-coding RNAs in ferroptosis regulation. , 2021, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[61]  Qiang He,et al.  miR-188-3p abolishes germacrone-mediated podocyte protection in a mouse model of diabetic nephropathy in type I diabetes through triggering mitochondrial injury , 2021, Bioengineered.

[62]  Y. Leng,et al.  Activation of NRF2/FPN1 pathway attenuates myocardial ischemia–reperfusion injury in diabetic rats by regulating iron homeostasis and ferroptosis , 2021, Cell Stress and Chaperones.

[63]  Lianju Shen,et al.  Di-(2-ethylhexyl) phthalate exposure leads to ferroptosis via the HIF-1α/HO-1 signaling pathway in mouse testes. , 2021, Journal of hazardous materials.

[64]  X. Ci,et al.  Leonurine alleviates ferroptosis in cisplatin‐induced acute kidney injury by activating the Nrf2 signalling pathway , 2021, British journal of pharmacology.

[65]  Ning Wang,et al.  Berberine improves insulin-induced diabetic retinopathy through exclusively suppressing Akt/mTOR-mediated HIF-1α/VEGF activation in retina endothelial cells , 2021, International Journal of Biological Sciences.

[66]  Xiaohe Xiao,et al.  Germacrone Attenuates Hepatic Stellate Cells Activation and Liver Fibrosis via Regulating Multiple Signaling Pathways , 2021, Frontiers in Pharmacology.

[67]  Haile Ma,et al.  Mangiferin: a review of dietary sources, absorption, metabolism, bioavailability, and safety. , 2021, Critical reviews in food science and nutrition.

[68]  Meitong Liu,et al.  Toward improved human health: Nrf2 plays a critical role in regulating ferroptosis. , 2021, Food & function.

[69]  H. Duan,et al.  PP2 Ameliorates Renal Fibrosis by Regulating the NF-κB/COX-2 and PPARγ/UCP2 Pathway in Diabetic Mice , 2021, Oxidative medicine and cellular longevity.

[70]  M. Akash,et al.  Neuroprotective potential of berberine in modulating Alzheimer's disease via multiple signaling pathways. , 2021, Journal of food biochemistry.

[71]  Ming-shun Zhao,et al.  Circ_0000491 Promotes Apoptosis, Inflammation, Oxidative Stress, and Fibrosis in High Glucose-Induced Mesangial Cells by Regulating miR-455-3p/Hmgb1 Axis , 2021, Nephron.

[72]  Asha Martin,et al.  Crocetin exerts hypocholesterolemic effect by inducing LDLR and inhibiting PCSK9 and Sortilin in HepG2 cells. , 2021, Nutrition research.

[73]  Xiang Wu,et al.  Long non-coding RNA CASC2 restrains high glucose-induced proliferation, inflammation and fibrosis in human glomerular mesangial cells through mediating miR-135a-5p/TIMP3 axis and JNK signaling , 2021, Diabetology & Metabolic Syndrome.

[74]  Ting Xu,et al.  Leonurine protects against ulcerative colitis by alleviating inflammation and modulating intestinal microflora in mouse models , 2021, Experimental and therapeutic medicine.

[75]  Chun-hua Song,et al.  Genetic variant of cyclooxygenase-2 in gastric cancer: More inflammation and susceptibility , 2021, World journal of gastroenterology.

[76]  D. Geng,et al.  Ginkgolide B protects against cognitive impairment in senescence-accelerated P8 mice by mitigating oxidative stress, inflammation and ferroptosis. , 2021, Biochemical and biophysical research communications.

[77]  Na Zhao,et al.  Crocetin suppresses gestational diabetes in streptozotocin-induced diabetes mellitus rats via suppression of inflammatory reaction. , 2021, Journal of food biochemistry.

[78]  Zhi-Wei Chen,et al.  Salusin-β participates in high glucose-induced HK-2 cell ferroptosis in a Nrf-2-dependent manner , 2021, Molecular medicine reports.

[79]  Lijun Xu,et al.  Baicalin Alleviates Oxidative Stress and Inflammation in Diabetic Nephropathy via Nrf2 and MAPK Signaling Pathway , 2021, Drug design, development and therapy.

[80]  Kang Du,et al.  Protective Effects of Dexazoxane on Rat Ferroptosis in Doxorubicin-Induced Cardiomyopathy Through Regulating HMGB1 , 2021, Frontiers in Cardiovascular Medicine.

[81]  J. Liao,et al.  LncRNA SOX2OT alleviates mesangial cell proliferation and fibrosis in diabetic nephropathy via Akt/mTOR-mediated autophagy , 2021, Molecular Medicine.

[82]  J. Moon,et al.  The role of inflammation in diabetic kidney disease , 2021, The Korean journal of internal medicine.

[83]  M. Fabbri,et al.  Noncoding RNA therapeutics — challenges and potential solutions , 2021, Nature reviews. Drug discovery.

[84]  H. Lee,et al.  Platycodin D attenuates airway inflammation via suppression Th2 transcription factor in a murine model of acute asthma , 2021, The Journal of asthma : official journal of the Association for the Care of Asthma.

[85]  Q. Han,et al.  Urinary sediment microRNAs can be used as potential noninvasive biomarkers for diagnosis, reflecting the severity and prognosis of diabetic nephropathy , 2021, Nutrition & Diabetes.

[86]  B. Budnik,et al.  Biliary excretion of excess iron in mice requires hepatocyte iron import by Slc39a14 , 2021, The Journal of biological chemistry.

[87]  Yingying Jiang,et al.  Berberine Slows the Progression of Prediabetes to Diabetes in Zucker Diabetic Fatty Rats by Enhancing Intestinal Secretion of Glucagon-Like Peptide-2 and Improving the Gut Microbiota , 2021, Frontiers in Endocrinology.

[88]  Jin-Yong Zhou,et al.  Total flavone of Abelmoschus Manihot improves colitis by promoting the growth of Akkermansia in mice , 2021, Scientific Reports.

[89]  D. Peng,et al.  Polygonatum sibiricum polysaccharide prevents depression-like behaviors by reducing oxidative stress, inflammation, and cellular and synaptic damage. , 2021, Journal of ethnopharmacology.

[90]  X. Su,et al.  Forsythoside A Alleviates High Glucose-Induced Oxidative Stress and Inflammation in Podocytes by Inactivating MAPK Signaling via MMP12 Inhibition , 2021, Diabetes, metabolic syndrome and obesity : targets and therapy.

[91]  Yichuan Hu,et al.  Sp1-mediated upregulation of Prdx6 expression prevents podocyte injury in diabetic nephropathy via mitigation of oxidative stress and ferroptosis. , 2021, Life sciences.

[92]  Yan Liu,et al.  HO-1-mediated ferroptosis as a target for protection against retinal pigment epithelium degeneration , 2021, Redox biology.

[93]  K. Nakano,et al.  Differentiation of Hodgkin lymphoma cells by reactive oxygen species and regulation by heme oxygenase‐1 through HIF‐1α , 2021, Cancer science.

[94]  E. Davidson,et al.  Characterization of Mice Ubiquitously Overexpressing Human 15-Lipoxygenase-1: Effect of Diabetes on Peripheral Neuropathy and Treatment with Menhaden Oil , 2021, Journal of diabetes research.

[95]  Xiaomeng Feng,et al.  Ferroptosis Enhanced Diabetic Renal Tubular Injury via HIF-1α/HO-1 Pathway in db/db Mice , 2021, Frontiers in Endocrinology.

[96]  T. Yoo,et al.  Characterization of ferroptosis in kidney tubular cell death under diabetic conditions , 2021, Cell Death & Disease.

[97]  Ying Zhao,et al.  HMGB1 regulates ferroptosis through Nrf2 pathway in mesangial cells in response to high glucose , 2021, Bioscience reports.

[98]  Yuan-Jian Song,et al.  Neuroprotective mechanisms of mangiferin in neurodegenerative diseases , 2021, Drug development research.

[99]  Hailong Wu,et al.  Transcriptome Analysis of the Inhibitory Effect of Sennoside A on the Metastasis of Hepatocellular Carcinoma Cells , 2021, Frontiers in Pharmacology.

[100]  Baogui Liu,et al.  Germacrone alleviates neurological deficits following traumatic brain injury by modulating neuroinflammation and oxidative stress , 2021, BMC Complementary Medicine and Therapies.

[101]  M. Uspenskaya,et al.  Mangiferin as New Potential Anti-Cancer Agent and Mangiferin-Integrated Polymer Systems—A Novel Research Direction , 2021, Biomolecules.

[102]  Ray-Jade Chen,et al.  Platycodin D reverses histone deacetylase inhibitor resistance in hepatocellular carcinoma cells by repressing ERK1/2-mediated cofilin-1 phosphorylation. , 2020, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[103]  Xiaofang Li,et al.  Calycosin: a Review of its Pharmacological Effects and Application Prospects , 2020, Expert review of anti-infective therapy.

[104]  Yu Jiang,et al.  Crocetin ameliorates chronic restraint stress-induced depression-like behaviors in mice by regulating MEK/ERK pathways and gut microbiota. , 2020, Journal of ethnopharmacology.

[105]  Shengjie Fan,et al.  Mangiferin and organ fibrosis: A mini review , 2020, BioFactors.

[106]  T. Kim,et al.  Platycodin D enhances LDLR expression and LDL uptake via down-regulation of IDOL mRNA in hepatic cells , 2020, Scientific Reports.

[107]  Quan Xia,et al.  Germacrone Regulates HBXIP-Mediated Cell Cycle, Apoptosis and Promotes the Formation of Autophagosomes to Inhibit the Proliferation of Gastric Cancer Cells , 2020, Frontiers in Oncology.

[108]  V. Viswanathan,et al.  Crosstalk between endoplasmic reticulum stress and oxidative stress in the progression of diabetic nephropathy , 2020, Cell Stress and Chaperones.

[109]  Sumei Zhao,et al.  LncRNA-antisense non-coding RNA in the INK4 locus promotes pyroptosis via miR-497/thioredoxin-interacting protein axis in diabetic nephropathy. , 2020, Life sciences.

[110]  Zhongming Wu,et al.  Inhibition of ferroptosis by up-regulating Nrf2 delayed the progression of diabetic nephropathy. , 2020, Free radical biology & medicine.

[111]  A. Suksamrarn,et al.  Germacrone Reduces Cisplatin-Induced Toxicity of Renal Proximal Tubular Cells via Inhibition of Organic Cation Transporter. , 2020, Biological & pharmaceutical bulletin.

[112]  Emad H M Hassanein,et al.  Umbelliferone attenuates gentamicin-induced renal toxicity by suppression of TLR-4/NF-κB-p65/NLRP-3 and JAK1/STAT-3 signaling pathways , 2020, Environmental Science and Pollution Research.

[113]  Xuyang Dai,et al.  The pharmacological activity of berberine, a review for liver protection. , 2020, European journal of pharmacology.

[114]  Junhua Li,et al.  Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study) , 2020, Nature Communications.

[115]  Wei Sun,et al.  Total Flavones of Abelmoschus manihot Remodels Gut Microbiota and Inhibits Microinflammation in Chronic Renal Failure Progression by Targeting Autophagy-Mediated Macrophage Polarization , 2020, Frontiers in Pharmacology.

[116]  Lin Sun,et al.  HIF‐1α ameliorates tubular injury in diabetic nephropathy via HO‐1–mediated control of mitochondrial dynamics , 2020, Cell proliferation.

[117]  Qiuhua Cao,et al.  Ferroptosis involves in renal tubular cell death in diabetic nephropathy. , 2020, European journal of pharmacology.

[118]  X. Shan,et al.  Study on the attenuated effect of Ginkgolide B on ferroptosis in high fat diet induced nonalcoholic fatty liver disease. , 2020, Toxicology.

[119]  Taotao Ma,et al.  Sennoside A prevents liver fibrosis by binding DNMT1 and suppressing DNMT1‐mediated PTEN hypermethylation in HSC activation and proliferation , 2020, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[120]  L. Chu,et al.  Crocetin attenuates the oxidative stress, inflammation and apoptosisin arsenic trioxide-induced nephrotoxic rats: Implication of PI3K/AKT pathway. , 2020, International immunopharmacology.

[121]  Wen-qian Wang,et al.  Leonurine protects against dexamethasone-induced cytotoxicity in pancreatic β-cells via PI3K/Akt signaling pathway. , 2020, Biochemical and biophysical research communications.

[122]  Yi Zhang,et al.  HMGB1 in inflammation and cancer , 2020, Journal of Hematology & Oncology.

[123]  H. Ding,et al.  p53/microRNA-214/ULK1 axis impairs renal tubular autophagy in diabetic kidney disease. , 2020, The Journal of clinical investigation.

[124]  P. Mandal,et al.  Role of advanced glycation end products and insulin resistance in diabetic nephropathy , 2020, Archives of physiology and biochemistry.

[125]  M. Kamal,et al.  Integrated Pathways of COX-2 and mTOR: Roles in Cell Sensing and Alzheimer’s Disease , 2020, Frontiers in Neuroscience.

[126]  J. Mitchell,et al.  Cyclooxygenases and the cardiovascular system. , 2020, Pharmacology & therapeutics.

[127]  J. M. Ferreira,et al.  Umbelliferone (7-hydroxycoumarin): A non-toxic antidiarrheal and antiulcerogenic coumarin. , 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[128]  T. Wen,et al.  NRF2, a Transcription Factor for Stress Response and Beyond , 2020, International journal of molecular sciences.

[129]  Chong-Feng Huang,et al.  Long Non-Coding RNA NEAT1 Regulates Pyroptosis in Diabetic Nephropathy via Mediating the miR-34c/NLRP3 Axis , 2020, Kidney and Blood Pressure Research.

[130]  A. Warowicka,et al.  Antiviral activity of berberine , 2020, Archives of Virology.

[131]  Zhiguang Sun,et al.  Gut Bacteria Selectively Altered by Sennoside A Alleviate Type 2 Diabetes and Obesity Traits , 2020, Oxidative medicine and cellular longevity.

[132]  Wajhul Qamar,et al.  Preclinical Evidence for the Pharmacological Actions of Glycyrrhizic Acid: A Comprehensive Review. , 2020, Current drug metabolism.

[133]  Zhaoyao Chen,et al.  Neuroprotective effect of Umbelliferone against Cerebral ischemia/Reperfusion induced neurological deficits: in-vivo and in-silico studies , 2020, Journal of biomolecular structure & dynamics.

[134]  B. Liu,et al.  Effects of thromboxane prostanoid receptor deficiency on diabetic nephropathy induced by high fat diet and streptozotocin in mice. , 2020, European journal of pharmacology.

[135]  Weiwei Yu,et al.  Crocetin Attenuates Sepsis-Induced Cardiac Dysfunction via Regulation of Inflammatory Response and Mitochondrial Function , 2020, Frontiers in Physiology.

[136]  M. Cooper,et al.  Targeting oxidative stress and anti-oxidant defence in diabetic kidney disease , 2020, Journal of Nephrology.

[137]  Zhijian Yang,et al.  Ginkgolide B inhibits hydrogen peroxide-induced apoptosis and attenuates cytotoxicity via activating the PI3K/Akt/mTOR signaling pathway in H9c2 cells , 2020, Molecular medicine reports.

[138]  K. Skalicka‐Woźniak,et al.  Xanthotoxin and umbelliferone attenuate cognitive dysfunction in a streptozotocin‐induced rat model of sporadic Alzheimer's disease: The role of JAK2/STAT3 and Nrf2/HO‐1 signalling pathway modulation , 2020, Phytotherapy research : PTR.

[139]  Y. Xing,et al.  Hirudin Reduces the Expression of Markers of the Extracellular Matrix in Renal Tubular Epithelial Cells in a Rat Model of Diabetic Kidney Disease Through the Hypoxia-Inducible Factor-1α (HIF-1α)/Vascular Endothelial Growth Factor (VEGF) Signaling Pathway , 2020, Medical science monitor : international medical journal of experimental and clinical research.

[140]  Donna D. Zhang,et al.  Breakdown of an Ironclad Defense System: The Critical Role of NRF2 in Mediating Ferroptosis. , 2020, Cell chemical biology.

[141]  C. Jiang,et al.  Glycyrrhizic acid as an adjunctive treatment for depression through anti-inflammation: A randomized placebo-controlled clinical trial. , 2020, Journal of affective disorders.

[142]  Guangyuan Gao,et al.  Mangiferin exert cardioprotective and anti-apoptotic effects in heart failure induced rats. , 2020, Life sciences.

[143]  T. Moos,et al.  Astrocytic expression of ZIP14 (SLC39A14) is part of the inflammatory reaction in chronic neurodegeneration with iron overload , 2020, Glia.

[144]  Shaoyan Zheng Protective effect of Polygonatum sibiricum Polysaccharide on D-galactose-induced aging rats model , 2020, Scientific Reports.

[145]  Xuelei Ruan,et al.  Metformin Reduces the Senescence of Renal Tubular Epithelial Cells in Diabetic Nephropathy via the MBNL1/miR-130a-3p/STAT3 Pathway , 2020, Oxidative medicine and cellular longevity.

[146]  Yongning Sun,et al.  Sennoside A Induces GLP-1 Secretion Through Activation of the ERK1/2 Pathway in L-Cells , 2020, Diabetes, metabolic syndrome and obesity : targets and therapy.

[147]  Yong-mei Liu,et al.  Platycodin D alleviates liver fibrosis and activation of hepatic stellate cells by regulating JNK/c-JUN signal pathway. , 2020, European journal of pharmacology.

[148]  S. Tang,et al.  Innate immunity in diabetic kidney disease , 2020, Nature Reviews Nephrology.

[149]  M. Kuo,et al.  High Glucose Induces Mesangial Cell Apoptosis through miR-15b-5p and Promotes Diabetic Nephropathy by Extracellular Vesicle Delivery. , 2020, Molecular therapy : the journal of the American Society of Gene Therapy.

[150]  T. Jia,et al.  Ginkgolide B improves multiterritory perforator flap survival by inhibiting endoplasmic reticulum stress and oxidative stress , 2019, Journal of investigative surgery : the official journal of the Academy of Surgical Research.

[151]  Shuo Su,et al.  Antiviral Activity of Germacrone against Pseudorabies Virus in Vitro , 2019, Pathogens.

[152]  Chengyan Zhou,et al.  Pharmacokinetic Comparisons of Mangiferin and Mangiferin Monosodium Salt in Rat Plasma by UPLC-MS/MS , 2019, Journal of Chemistry.

[153]  A. Ostadrahimi,et al.  The effect of crocetin supplementation on markers of atherogenic risk in patients with coronary artery disease: a pilot, randomized, double-blind, placebo-controlled clinical trial. , 2019, Food & function.

[154]  Hoda Atef,et al.  Renoprotective effect of calycosin in high fat diet-fed/STZ injected rats: Effect on IL-33/ST2 signaling, oxidative stress and fibrosis suppression. , 2019, Chemico-biological interactions.

[155]  K. Vasquez,et al.  Interactions of high mobility group box protein 1 (HMGB1) with nucleic acids: Implications in DNA repair and immune responses. , 2019, DNA repair.

[156]  Xiao-Ming Yin,et al.  Role of High-Mobility Group Box-1 in Liver Pathogenesis , 2019, International journal of molecular sciences.

[157]  Haiying Jin,et al.  Mangiferin ameliorates gestational diabetes mellitus-induced placental oxidative stress, inflammation and endoplasmic reticulum stress and improves fetal outcomes in mice. , 2019, European journal of pharmacology.

[158]  Wei Sun,et al.  Bupleurum polysaccharides ameliorated renal injury in diabetic mice associated with suppression of HMGB1-TLR4 signaling. , 2019, Chinese journal of natural medicines.

[159]  S. Dixon,et al.  GPX4 at the Crossroads of Lipid Homeostasis and Ferroptosis , 2019, Proteomics.

[160]  R. Nishimura,et al.  Unraveling the Role of Inflammation in the Pathogenesis of Diabetic Kidney Disease , 2019, International journal of molecular sciences.

[161]  Ivo F Scheiber,et al.  Manganese Uptake by A549 Cells is Mediated by Both ZIP8 and ZIP14 , 2019, Nutrients.

[162]  B. Honoré,et al.  The zinc transporter Zip14 (SLC39a14) affects Beta-cell Function: Proteomics, Gene expression, and Insulin secretion studies in INS-1E cells , 2019, Scientific Reports.

[163]  Uraporn Vongvatcharanon,et al.  Effect of glabridin on collagen deposition in liver and amelioration of hepatocyte destruction in diabetes rats , 2019, Experimental and therapeutic medicine.

[164]  Deqing Sun,et al.  Polysaccharides from Polygonatum sibiricum Delar. ex Redoute induce an immune response in the RAW264.7 cell line via an NF-κB/MAPK pathway , 2019, RSC advances.

[165]  Ting-ting Zhao,et al.  Research Progress of Glycyrrhizic Acid on Antiviral Activity. , 2019, Mini reviews in medicinal chemistry.

[166]  Xiao-Lan Cheng,et al.  Umbelliferone ameliorates renal function in diabetic nephropathy rats through regulating inflammation and TLR/NF-κB pathway. , 2019, Chinese journal of natural medicines.

[167]  Bo Yang,et al.  Role of tea polyphenols in delaying hyperglycemia-induced senescence in human glomerular mesangial cells via miR-126/Akt–p53–p21 pathways , 2019, International Urology and Nephrology.

[168]  Matthew D. Dun,et al.  Differential cell death decisions in the testis: evidence for an exclusive window of ferroptosis in round spermatids. , 2019, Molecular human reproduction.

[169]  Qiang He,et al.  Inhibition of high mobility group box 1 (HMGB1) attenuates podocyte apoptosis and epithelial‐mesenchymal transition by regulating autophagy flux , 2019, Journal of diabetes.

[170]  H. Ashida,et al.  Glabridin inhibits dexamethasone-induced muscle atrophy. , 2019, Archives of biochemistry and biophysics.

[171]  D. Tang,et al.  The release and activity of HMGB1 in ferroptosis. , 2019, Biochemical and biophysical research communications.

[172]  Ying-ying Zhang,et al.  Calycosin Ameliorates Diabetes-Induced Renal Inflammation via the NF-κB Pathway In Vitro and In Vivo , 2019, Medical science monitor : international medical journal of experimental and clinical research.

[173]  M. Conrad,et al.  Role of GPX4 in ferroptosis and its pharmacological implication. , 2019, Free radical biology & medicine.

[174]  A. Paterson,et al.  Risk Factors for Kidney Disease in Type 1 Diabetes , 2019, Diabetes Care.

[175]  D. Swinkels,et al.  Iron uptake by ZIP8 and ZIP14 in human proximal tubular epithelial cells , 2019, BioMetals.

[176]  Ryan M. Anderson,et al.  Platelet-type 12-lipoxygenase deletion provokes a compensatory 12/15-lipoxygenase increase that exacerbates oxidative stress in mouse islet β cells , 2019, The Journal of Biological Chemistry.

[177]  Dae-Hee Lee,et al.  Effect of sulfation and partial hydrolysis of polysaccharides from Polygonatum sibiricum on immune-enhancement. , 2019, International journal of biological macromolecules.

[178]  Honglei Ren,et al.  Iron toxicity, lipid peroxidation and ferroptosis after intracerebral haemorrhage , 2019, Stroke and Vascular Neurology.

[179]  Donna D. Zhang,et al.  NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis , 2019, Redox biology.

[180]  Yang Zhang,et al.  Aspirin attenuates podocyte injury in diabetic rats through overriding cyclooxygenase-2-mediated dysregulation of LDL receptor pathway , 2019, International Urology and Nephrology.

[181]  K. Ahn,et al.  Platycodin D, a novel activator of AMP-activated protein kinase, attenuates obesity in db/db mice via regulation of adipogenesis and thermogenesis. , 2019, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[182]  G. Rao,et al.  Emerging role of 12/15-Lipoxygenase (ALOX15) in human pathologies. , 2019, Progress in lipid research.

[183]  Xiaodong Yang Design and optimization of crocetin loaded PLGA nanoparticles against diabetic nephropathy via suppression of inflammatory biomarkers: a formulation approach to preclinical study , 2019, Drug delivery.

[184]  C. Zeng,et al.  Increased urinary miR-196a level predicts the progression of renal injury in patients with diabetic nephropathy. , 2018, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[185]  A. Ortiz,et al.  Inflammation in Diabetic Kidney Disease , 2018, Nephron.

[186]  Ying He,et al.  Aquaporins Alteration Profiles Revealed Different Actions of Senna, Sennosides, and Sennoside A in Diarrhea-Rats , 2018, International journal of molecular sciences.

[187]  B. Zhang,et al.  Leonurine ameliorates adriamycin-induced podocyte injury via suppression of oxidative stress , 2018, Free radical research.

[188]  W. Maret,et al.  Prolonged stimulation of insulin release from MIN6 cells causes zinc depletion and loss of β-cell markers. , 2018, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[189]  W. Lu,et al.  Renoprotection of dapagliflozin in human renal proximal tubular cells via the inhibition of the high mobility group box 1‑receptor for advanced glycation end products‑nuclear factor‑κB signaling pathway. , 2018, Molecular medicine reports.

[190]  Fei Shang,et al.  Berberine Could Ameliorate Cardiac Dysfunction via Interfering Myocardial Lipidomic Profiles in the Rat Model of Diabetic Cardiomyopathy , 2018, Front. Physiol..

[191]  Xueling Ma,et al.  The Pathogenesis of Diabetes Mellitus by Oxidative Stress and Inflammation: Its Inhibition by Berberine , 2018, Front. Pharmacol..

[192]  Yan Li,et al.  Ginkgolide B exerts anti-inflammatory and chondroprotective activity in LPS-induced chondrocytes. , 2018, Advances in clinical and experimental medicine : official organ Wroclaw Medical University.

[193]  D. Swinkels,et al.  Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease , 2018, Scientific Reports.

[194]  G. Wang,et al.  Metastatic cancers promote cachexia through altered zinc homeostasis in skeletal muscle , 2018, Nature Medicine.

[195]  A. Agarwal,et al.  Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells. , 2018, American journal of physiology. Renal physiology.

[196]  P. Rossing,et al.  Prognosis and treatment of diabetic nephropathy: Recent advances and perspectives. , 2018, Nephrologie & therapeutique.

[197]  Jennifer Beatriz Silva Morais,et al.  Zinc and Insulin Resistance: Biochemical and Molecular Aspects , 2018, Biological Trace Element Research.

[198]  Lifang Ye,et al.  Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/TACE signalling pathway activity in rats , 2017, Pharmaceutical biology.

[199]  Yuan Li,et al.  Glycyrrhizic Acid Prevents Diabetic Nephropathy by Activating AMPK/SIRT1/PGC-1α Signaling in db/db Mice , 2017, Journal of diabetes research.

[200]  M. Delgado-Rodríguez,et al.  Systematic review and meta-analysis. , 2017, Medicina intensiva.

[201]  Aikseng Ooi,et al.  The Roles of NRF2 in Modulating Cellular Iron Homeostasis , 2017, Antioxidants & redox signaling.

[202]  Y. Yoshimoto,et al.  Lipoxygenase‐mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3 , 2017, Cancer science.

[203]  D. Yoon,et al.  Peroxiredoxin 6 overexpression attenuates lipopolysaccharide-induced acute kidney injury. , 2017, Oncotarget.

[204]  R. Bertrand Iron accumulation, glutathione depletion, and lipid peroxidation must occur simultaneously during ferroptosis and are mutually amplifying events. , 2017, Medical hypotheses.

[205]  Chengyong He,et al.  Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1 , 2017, Theranostics.

[206]  Mitsuo Kato,et al.  Epigenetic Histone Modifications Involved in Profibrotic Gene Regulation by 12/15-Lipoxygenase and Its Oxidized Lipid Products in Diabetic Nephropathy. , 2016, Antioxidants & redox signaling.

[207]  J. Dominguez,et al.  Renal iron overload in rats with diabetic nephropathy , 2015, Physiological reports.

[208]  Jian-jun Zhang,et al.  Umbelliferone exhibits anticancer activity via the induction of apoptosis and cell cycle arrest in HepG2 hepatocellular carcinoma cells. , 2015, Molecular medicine reports.

[209]  D. Johnstone,et al.  Renal peroxiredoxin 6 interacts with anion exchanger 1 and plays a novel role in pH homeostasis , 2015, Kidney international.

[210]  Anlin Peng,et al.  Inhibitory effect of leonurine on the formation of advanced glycation end products. , 2015, Food & function.

[211]  Haichao Wang,et al.  HMGB1 in health and disease. , 2014, Molecular aspects of medicine.

[212]  A. Walch,et al.  Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice , 2014, Nature Cell Biology.

[213]  Mark E Molitch,et al.  Diabetic Kidney Disease: A Report From an ADA Consensus Conference , 2014, Diabetes Care.

[214]  Hailing Li,et al.  Iron Increases Diabetes-Induced Kidney Injury and Oxidative Stress in Rats , 2014, Biological Trace Element Research.

[215]  Matthew E. Welsch,et al.  Regulation of Ferroptotic Cancer Cell Death by GPX4 , 2014, Cell.

[216]  Cuicui Zhang,et al.  Role of expression of endothelin-1 and angiotensin-II and hypoxia-inducible factor-1α in the kidney tissues of patients with diabetic nephropathy. , 2013, Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia.

[217]  Feihua Wu,et al.  Hypoglycemic effects of glabridin, a polyphenolic flavonoid from licorice, in an animal model of diabetes mellitus. , 2013, Molecular medicine reports.

[218]  Yuichiro J Suzuki,et al.  Faculty Opinions recommendation of Ferroptosis: an iron-dependent form of nonapoptotic cell death. , 2012 .

[219]  K. Bennell,et al.  Recent advances and perspectives , 2012 .

[220]  A. Fisher,et al.  Peroxiredoxin 6: a bifunctional enzyme with glutathione peroxidase and phospholipase A₂ activities. , 2011, Antioxidants & redox signaling.

[221]  P. Hasanein Glabridin as a major active isoflavan from Glycyrrhiza glabra (licorice) reverses learning and memory deficits in diabetic rats. , 2011, Acta physiologica Hungarica.

[222]  B. Ramesh,et al.  Antihyperlipidemic and antidiabetic effects of umbelliferone in streptozotocin diabetic rats. , 2005, The Yale journal of biology and medicine.

[223]  S. Adler,et al.  Novel interactions between TGF-{beta}1 actions and the 12/15-lipoxygenase pathway in mesangial cells. , 2005, Journal of the American Society of Nephrology : JASN.

[224]  C. Dodia,et al.  1-Cys Peroxiredoxin, a Bifunctional Enzyme with Glutathione Peroxidase and Phospholipase A2 Activities* , 2000, The Journal of Biological Chemistry.

[225]  Xueyuan Bai,et al.  Autophagy and Diabetic Nephropathy. , 2020, Advances in experimental medicine and biology.

[226]  Fa-Qian Shen,et al.  Advances in pharmacological activities and mechanisms of glycyrrhizic acid. , 2019, Current medicinal chemistry.

[227]  D. Holdstock Past, present--and future? , 2005, Medicine, conflict, and survival.

[228]  M. Friedman Biochemical and molecular aspects , 1977 .

[229]  Mechanistic insights , 2022 .